AIDS Patients Living Longer,
But Vaccine Remains Elusive

It’s been almost exactly 25 years since the term “Acquired Immune Deficiency Syndrome” was used for the first time at a meeting in Washington, D.C., in July 1982.

By August, the new term AIDS was being used in scientific journals, and it was officially defined by the Centers for Disease Control and Prevention in September.

But having a name for the disease didn’t mean there was a treatment for it. Indeed, it would be five more years before AZT (zidovudine), the iconic first drug to prolong the lives of people infected with HIV, would be approved by the Food and Drug Administration. Over the next 20 years, an extraordinary international research effort would lead to the development of more than 60 antiretroviral drugs—drugs that slow down the replication of HIV in the body. (Some 27 of those drugs are in use today.)

Today, although there is no cure, the gold-standard HAART (highly active antiretroviral therapy, or a combination of three or more anti-HIV drugs), along with other, newer research developments have changed the face of the future for people with AIDS—at least those in the Western world who have access to these state-of-the-art therapies. These drug “cocktails” are thought to increase survival time by between four years to 12 years—a result that many cancer drug researchers only dream of presenting at the next clinical oncology meeting.

Between 1995 and 2002, scientists at the Johns Hopkins School of Public Health concluded that HAART therapies saved between 33,000 and 43,000 lives in the United States. Indeed, U.S. AIDS deaths dropped from more than 51,000 in 1995 to some 38,000 in 1996 with the introduction of these combination therapies. That’s the up side.

The down side: HAART isn’t a cure. If it increases survival time by four to 12 years, what happens at the end of that stretch of time? Most people are infected with HIV at an age when they otherwise would have expected to live a lot longer. Although many doctors will talk about the transformation of AIDS into a “chronic illness,” the fact remains that it still kills some 15,000 people a year in the United States alone. And after the dramatic declines of the late 1990s, the rate of HIV infection and the rate of death from AIDS in the United States have both hit a plateau, with some years even showing small increases.

Reservoirs of HIV persist in the body even after years of antiretroviral therapy, which can ultimately leave patients with no remaining treatment options as the cunning virus develops resistance to one drug after another.

In March, promising new results were announced for two new drugs—one an entry inhibitor called maraviroc, which binds to a protein on the membrane of CD4 immune cells, where reservoirs of the virus often lurk, and prevents the virus from infecting healthy cells. The other, raltegravir, is the first of an entirely new class of HIV drugs called integrase inhibitors, which prevent the virus’s genetic material from becoming part of the host’s DNA. Both drugs zapped patients’ viral loads to near-undetectable levels and have been given “fast track” status by the FDA.

But the holy grail of AIDS research is still a vaccine. In 1997, President Bill Clinton set the goal of developing an AIDS vaccine within the next 10 years. The date has arrived but the goal hasn’t, despite a global investment of billions upon billions of dollars, largely through the International AIDS Vaccine Initiative (IAVI), established in 1996 and still the only organization in the world focused solely on the development of an AIDS vaccine.

Some projects have come tantalizingly close, only to fail in human trials. There are currently some 30 clinical trials of vaccines under way in 24 countries, according to the IAVI.

In an article in the New England Journal of Medicine in May, AIDS research pioneer Anthony Fauci, who now directs the National Institute of Allergy and Infectious Diseases, explained that a preventive vaccine—like those given to children for measles, mumps and chicken pox—may be harder to achieve for AIDS than for other diseases because of the virus’s mutability. “First-generation” AIDS vaccines, he said, might not induce a response that prevents infection, but instead could knock down virus levels and help block transmission.

Many scientists see vaccine development as essential to truly ending the AIDS epidemic—particularly in the developing world, where unlike the United States, rates of HIV infection have climbed, not dropped, over the past decade. In sub-Saharan Africa, which has been harder hit by AIDS and HIV than any other area of the world, some 24.5 million people were living with HIV at the end of 2005, with 2.7 million becoming infected in that year alone. An estimated 2 million of those have died.

There have been recent drops in the prices of antiretroviral drugs in these countries. According to the international AIDS charity AVERT, a year’s course of medication that once cost thousands of dollars can now be had for a few hundred dollars at most. Nevertheless, problems such as infrastructure, supply chains, trained providers and the mere fact that even a few hundred dollars can be a small fortune in many countries have kept access to these drugs in sub-Saharan Africa and other such areas limited. Indeed, in December 2006, some 7,100,000 people in developing countries needed antiretroviral drugs, but only 2,015,000 were getting them—just 28 percent of the population in need.

“We must find better HIV prevention technologies. A vaccine remains the best hope for ending the epidemic,” said Dr. Seth Berkley, founder of IAVI. “That is why it is imperative that we focus the best tools of science and establish better models for conducting AIDS vaccine research.”

Gina Shaw is the medical writer for The Washington Diplomat.

HAART Cocktail
The four key ingredients in a HAART cocktail—which doctors can mix and remix to suit their patients’ needs—include:

Nucleoside/Nucleotide Reverse Transcriptase Inhibitors:
This is the family to which AZT belongs and is the first group of drugs available to treat HIV infection. They interfere with a process called reverse transcription, which the HIV protein uses to make new copies of the virus. Most regimens include at least two of these drugs.

Non-Nucleoside Reverse Transcriptase Inhibitors:
These drugs operate slightly differently from the nucleoside “nukes,” but their goal is the same: Block the reverse transcriptase protein and interrupt replication.

Entry and Fusion Inhibitors:
These are the new kids on the antiretroviral block. Only one has been approved by the FDA thus far—Fuzeon (enfuvirtide)—but more are likely to follow. These drugs are like gatekeepers, inhibiting the ability of the virus to infect a healthy cell.